Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cold-insoluble globulin is normally present in plasma and serum at concentrations of 27.52 +/- 4.60 and 23.46 +/- 5.18 mg/dl, respectively (means +/- SD). The concentration of CIg in blood samples was significantly decreased in DIC syndromes (14.69 +/- 6.55 mg/dl; p less than 0.001). A strong, positive correlation was found with AT-III (r = 0.68) and a less striking one with Plg. Although alpha 2-PI was shown to be significantly decreased in DIC syndromes (p less than 0.001), a weak, inverse correlation was found between CIg and alpha 2-PI (r = -0.29). Immunologically cross-reactive substances were found to be widely distributed in association with the cells and tissues of mesenchymal origin, including fibroblasts, adipose cells, smooth muscle cells, and basement membranes. The glomerular basement membrane was an exception and is currently believed to be of different origin. In the kidney, fluorescence was found in the mesangium. Cold-insoluble globulin is also present as a component of cryofibrinogen that forms a solid gel at low temperatures. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed that CIg in this fraction was rather homogeneous. Although closely migrating doublets were occasionally seen in the 440,000-dalton region on gels of unreduced samples, monomeric derivatives with a molecular weight of 220,000 or less, which have been claimed to occur in circulating plasma, were not observed. Thus, intact dimeric CIg appears to be the form of the molecule that complexes with fibrinogen. Cold-insoluble globulin is the fraction that was shown to exist as an independent entity from fibrinogen at an ambient temperature by immunoelectrophoresis and ultracentrifugation. However, very rapid formation of highly polymerized complexes in the sol phase at low temperatures was manifested by the finding of a sharp increase in light-scattering intensity using the technique of quasielastic light scattering. A control study on a mixture of normal CIg and fibrinogen disclosed no appreciable change in the temperature range between 37 and 8.5 degrees C. A comparative study on a mixture of cryofibrinogen-derived CIg and normal fibrinogen revealed an intermediate light-scattering pattern. After 2 hr at 8 degrees C, this mixture reached a state of equilibrium, where no further polymerization occurred. The secondary structures of normal and cryofibrinogen-derived CIg, determined by circular dichroism, showed no appreciable difference. A noteworthy finding was the almost complete absence of alpha-helices and a relatively high proportion of beta-structure in both forms of CIg. Amino termini of the fibrinogen moiety of cryofibrinogen were found to consist of alanine, tyrosine, and a small quantity of aspartic acid, consistent with the NH2 terminal moiety composition of normal fibrinogen but not of soluble fibrin monomer complex.
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PMID:Distribution of cold-insoluble globulin in plasma and tissues. 29 82

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel-electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.
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PMID:Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique. 50 38

To test the possibility that a functionally abnormal fibrinogen may exist in some patients with liver disease, we studied the plasma and purified fibrinogens of five patients whose plasma thrombin times were prolonged at least 40% over normal controls. In no patient was there evidence of disseminated intravascular coagulation and/or fibrinolysis. No abnormalities were detected by immunoelectrophoresis of plasmas or purified fibrinogens. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced patient fibrinogens showed normal mobility and amount of Aalpha, Bbeta, and gamma chains. Alkaline polyacrylamide gel electrophoresis and gradient elution, DEAE-cellulose chromatography of admixtures of radio-iodinated patient (125)I-fibrinogen and normal (131)I-fibrinogen showed identical mobility in the gel and simultaneous elution from the column, respectively. Thrombin and Reptilase (Abbott Scientific Products Div., Abbott Laboratories, South Pasadena, Calif.) times of purified patient fibrinogens were prolonged, and calcium ions improved but did not completely correct these defects. Increasing amounts of thrombin progressively shortened the clotting times of patient fibrinogens but not to the level of normal. Addition of equal amounts of patient fibrinogen to normal fibrinogen resulted in a prolongation of the thrombin time of the normal protein. Thrombin-induced fibrinopeptide release was normal. Fibrin monomers prepared from patient plasmas and purified fibrinogens demonstrated impaired aggregation at low (0.12) and high (0.24) ionic strength. These studies demonstrate that some patients with liver disease and prolonged plasma thrombin times have a dysfibrinogenemia functionally characterized by an abnormality of fibrin monomer polymerization.
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PMID:Dysfibrinogenemia associated with liver disease. 87 92

The sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombin inhibition is impaired in plasma of sick neonates. 137 86

Although the possible occurrence of systemic fibrinogenolysis has been suggested in patients with metastasising prostatic cancer (MPC), direct evidence is lacking. We report on a patient with MPC whose laboratory data were consistent with hyperfibrinolysis: marked decrease of alpha 2-antiplasmin (AP) level (less than 50% of normal), increase of plasmin-alpha 2-antiplasmin complex, D-fragment of fibrin and fibrinogen degradation products [FDP(D)] and cross-linked fibrin degradation products (XDP). The patient neither showed laboratory nor clinical evidence for consumption coagulopathy except for a slight increase in thrombin-antithrombin III complex level. Immunoblotting of the patient's serum using an anti-fibrinogen antibody revealed the presence of a 250 kDa protein in addition to DD fragments. Following reduction of this protein by 2-mercaptoethanol after extraction from SDS-PAGE gel, gamma-chain of fibrinogen (47 kDa) was found by immunoblotting using a monoclonal antibody recognising a 86-302 residue of the gamma-remnant of fibrinogen. Moreover, the 250 kDa protein did not bind to Sepharose 4B to which a monoclonal antibody recognising the N-terminus of fragment D was conjugated. These findings indicated that this protein was not fragment DY, but rather fibrinogen fragment X. With the retraction of the prostatic tumour by an effective therapy, the patient's AP level increased gradually. When the plasma AP level rose to 60% of normal, the fragment X was no longer detectable. These findings suggested that systemic fibrinogenolysis occurred in the patient with MPC only when AP levels were markedly decreased.
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PMID:Direct evidence for systemic fibrinogenolysis in a patient with metastatic prostatic cancer. 151 30

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis of plasma thrombomodulin concentrate revealed that four degraded forms of thrombomodulin with different molecular weights are present in plasma. Plasma concentrations of thrombomodulin in patients with various diseases were measured by two methods of enzyme-linked immunosorbent assay using monoclonal antibodies. One method measures intact thrombomodulin and degraded forms of thrombomodulin; the other does not detect the two smaller degraded forms of thrombomodulin present in plasma. The results indicated that thrombomodulin was increased in the circulating blood of patients with disseminated intravascular coagulation syndrome, pulmonary thromboembolism, adult respiratory distress syndrome, chronic renal failure, or acute hepatic failure. The different values obtained by the two methods indicate that the increase of plasma thrombomodulin found in these patients was mainly due to an increase of the smaller fragments of degraded forms, suggesting that the release of thrombomodulin from endothelial cells was accelerated in various disease states by proteolytic activity generated on the surface of the endothelium and may be removed from the circulation mostly by the kidneys and liver.
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PMID:Plasma thrombomodulin in health and diseases. 217 34

SDS-PAGE and immunoblot technique with anti-FDP-D, -FDP-E, -fibrinogen antibody or anti-FDP-DD monoclonal antibody were applied to analyze FDP fragments prepared from cross-linked fibrin and fibrinogen with plasmic digestion in vitro. FDP fragments of DY(260K), DD(187K), X(245K), Y(166K), D(77K, 97K), E1(58K), E2(46K) and E3(40K) were identified from data of molecular weight and reactivity to four antibodies referred to reports of other investigators. Serum FDP fragments from five DIC suspected patients were analyzed by the same methods. In two patients' sera, DD fragment was a main component, and in the other three patients' sera, D fragment was a main fraction. Proportions of high molecular weight fragments of FDP were considerably different in patients' sera. Appearance of D fragment in our cases was considered to be derived from unstable fibrin (fibrin monomer and dimer) rather than from fibrinogen. Molecular weight of DD fragments from patients' sera had heterogeneity (160 approximately 180K), and the values were different from that (187K) prepared from cross-linked fibrin. In conclusion, SDS-PAGE and immunoblot analysis of serum fragments of FDP will be an useful technique to investigate the clinical and pathological condition of DIC.
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PMID:[Analysis of cross-linked fibrin and fibrinogen degradation products with SDS-PAGE and immunoblot]. 232 22

Protein C (PC) is a vitamin K-dependent serine protease which functions as the central regulatory protein with both anticoagulant and profibrinolytic properties. The PC levels in healthy term newborns are approximately one third of adult levels. Severely decreased levels of PC are seen in sick term and preterm infants. These neonates appear to have an increased incidence of thrombosis. Undetectable levels of PC are found in homozygous PC deficient infants with DIC and purpura fulminans symptoms. In this present study we report the composition and distribution of PC in term newborn and compare the results with adult values. Plasma was obtained from placental cord blood of 20 healthy term (38-42 weeks gestation) infants. PC was immunopurified, run on SDS-PAGE, and immuno-blotted. The composition of the PC molecule in neonatal plasma is identical to that seen in adults. Using densitometry to determine the distribution of the PC components, we observed a 2-fold increase in single chain PC in the neonate as compared to the adult. In the neonate, there was an inverse correlation between the level of total PC antigen and the amount of single chain. These findings suggest the possibility that the processing of PC may be developmentally influenced.
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PMID:Neonatal protein C: molecular composition and distribution in normal term infants. 259 75

Metastatic spread of malignant tumor appears to correlate with activation of the fibrolytic system. The role of fibrinolysis in growth and metastasis was examined in Lewis lung carcinoma of mice. The inhibition of fibrinolysis or proteases decreased the primary tumor growth and pulmonary metastasis, whereas the activation of fibrinolysis or proteases increased the number of metastatic foci in the lung. Electronmicroscopically, thrombus formation in the primary site prevented tumor invasion and metastasis formation. Plasminogen activator (PA) content of excised tumors was determined by SDS-PAGE, and major PA was found to be urokinase (UK) type. Immunohistochemical study with specific antisera was done. When tumor cells possessed a high level of UK, laminin and type IV collagen, components of the basement membrane, disappeared from tumor tissues. These findings suggest that PA through protease cascade plays a role in tumor invasion and metastasis. Clinically, patients with advanced cancer are usually in a hypercoagulable state with elevated fibrinogen, and fibrin deposition around tumor mass is a serious problem in cancer chemotherapy. UK infusion prior to 5-fluorouracil increased tissue concentration of antitumor agent. However, development of consumption coagulopathy characterized by progression from hypercoagulable state to disseminated intravascular coagulation has also been found in several cases.
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PMID:[Tumor metastasis and the fibrinolytic system]. 273 23

Purified fibrinogen as well as normal plasma, or plasma from patients with DIC or undergoing streptokinase(SK)-therapy was subjected to 1D- and 2D SDS-electrophoresis under reducing conditions. The pattern was revealed either by Coomassie-staining or immunostaining after Western-blotting and then compared. The use of polyclonal antibodies to fibrinogen as well as two monoclonal anti-bodies reacting with FPA and C-terminal part of the A alpha-chain confirmed immunologically the previously reported molecular weight heterogeneity of the A alpha-chain of the fibrinogen molecule as being a constituent of normal plasma, and lead to the following conclusions: 1. The MW-heterogeneity is observed in the fibrinogen pool of normal plasma as well as in DIC-plasma, SK-plasma and in purified fibrinogen, being the least noticeable in normal plasma and most advanced in SK-plasma. Patterns obtained using immunostaining with monoclonal anti-FPA confirm that the MW-heterogeneity of fibrinogen is mainly due to C-terminal degradation of the A alpha-chain. 2. Numerous A alpha-chain remnants (at least 9), with intact N-terminal ends, are found to be present in normal plasma, with a MW range from 66,200 to 36,000 Da, demonstrating that each of the "classical" HMW, LMW, LMW' subgroups consist of fibrinogen molecules which are very heterogeneous. 3. Two populations of A alpha-chains in purified fibrinogen and in fibrinogen in plasma react with the C-terminal specific Mab G-8. This is in contrast to the findings in plasma from streptokinase-treated patients, where several bands of lower molecular weights than the gamma-chain can be seen, suggesting the presence of free, circulating A-alpha chains split in the N-terminal half of the chain beyond the last inter-chain disulphide bond. 4. 2D electrophoresis disclosed substantial deviations in the patterns obtained with DIC-plasma, SK-plasma and with fibrinogen purified by beta-alanine-precipitation from that observed with normal plasma. The present technique allows selective characterization of fibrinogen independently of the other proteins present in plasma and offers extreme sensitivity.
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PMID:Immunovisualization of fibrinogen A alpha-chain heterogeneity in normal plasma and plasma from patients with DIC or on streptokinase therapy. 322 83


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